Usually
DNA analysis tells a story of the future or recent past. In hospitals,
genetic tests reveal patients’ risk for disease and in court rooms it
helps solve crimes. But for students of history, DNA can also unlock the
door to the distant past.

One unorthodox research team, comprised of Danish biochemists and archeologists,
is analyzing genetic material from ancient bones to solve the mystery
of why many Northern Europeans are resistant to HIV.

The 32D mutation increases in frequency with distance from the Mediterranean.
The plague began in Sicily and spread north to hit Scandinavia around
1350.

Biochemist Jesper Eugen-Olsen leads a team at Copenhagen’s Hvidovre Hospital
that investigates the disease mechanisms of HIV. But he also has an abiding
interest in history. He has worked for years with a genetic mutation that
confers immunity to HIV. To delve into the history of this mutation, Eugen-Olsen
teamed up with archeologist and carbon-dating expert Kaare Lund Rasmussen,
of the Danish National Museum.

This mutationcalled 32Dis a deletion of 32 DNA bases in a
gene encoding CCR5, a protein that allows HIV to enter cells. Two copies
of the mutation confer complete protection against HIV. A single copy
confers only partial protection. Individuals inheriting only one copy
of the mutation can become infected, but they stay symptom free considerably
longer than those with no mutations of the CCR5 gene.

"It always puzzled scientists in the field that the mutation never
occurs in Asian or African populations, but only among European Caucasians,"
Eugen-Olsen says. Within Europe, the mutation shows a characteristic gradient,
with an extremely high prevalence in the North tapering off towards the
Mediterranean. So while only eight of 100 Southern Italians carries a
copy of 32D, one in every four Danes has it.

From its distribution, most scientists agree that 32D emerged in Northern
Europe. Because 32D is identical in all carriers, the mutation probably
arose in one person, an ancestor to all those who now carry the mutation.
But when did that ancestor live? For the mutation to be widespread in
the Danish population, it must have arisen long before the known advent
of HIV. In order to have spread so successfully, it must at some point
have provided its carriers with a selective advantage, Eugen-Olsen reasons.
"Most likely it conferred immunity to one or more epidemics that
selectively wiped out people with a normal CCR5 gene."

One hypothesis holds that this epidemic was the bubonic plague of the
Middle Ages, which killed a third of Europe’s population. According to
this hypothesis, 32D would have protected carriers against plague.

The Danes doubt this conclusion. "Examining the history of the plague
made us dispute this," says Rasmussen. The Black Death began in Sicily
and spread north to hit Scandinavia around 1350. This course would predict
that the prevalence of 32D should be higher in the south, just the opposite
of its observed prevalence. Furthermore, molecular evidence remains inconclusive.
Using two different molecular methods for dating mutations, two American
teams have analyzed human DNA attempting to determine when 32D first arose.
But their estimates vary widely. One group came up with a figure of 700
years and the other with 2,000.

Eugen-Olsen and Rasmussen are taking an alternative route. Building on
the assumption that 32-D arose in Scandinavia, they are trying to nail
down the time of its explosive spread by examining DNA from bones found
in Denmark and dating from the period between the last ice age (around
8,000 BC) and 1950.

In particular, the scientists have their eyes on a Mesolithic period
of massive cultural change, between 1,800 and 2,600 BC. Archeological
evidence shows that the shift dramatically changed weapons, ornamentation,
farming methods and burial customs. Archeologists call the new culture
the Single Grave Culture, and have speculated that massive migrations
brought on the change.

The Danish team is the first to suggest instead that one or more epidemics
caused the cultural change. According to Rasmussen, an epidemic decimating
the stone age population could explain the archeological observations
as well as the distribution of 32-D. "There is support in the fact
that the distribution of the Single Grave Culture in Northern and Middle
Europe matches that of the high prevalence of 32D."

Although still a work in progress, the Danish project is already turning
up evidence against the reigning Black Death hypothesis. After extracting
DNA from some 50 ancient bone tissue samples, the researchers have identified
the mutation in specimens predating the middle ages. "Using simple
statistics, this tells us that the mutation was highly prevalent in Denmark
before the bubonic plague," says Eugen-Olsen.

If the complete DNA analysis supports his theory of Mesolithic epidemics,
Eugen-Olsen hopes to identify those microbes that might have been responsible.
In what he calls a fishing expedition, the group will grow immune cells
from the blood of people with and without the 32D mutation, then challenge
the cells with a range of human pathogens. "Microbes that kill normal
cells but leave cells from mutation carriers unharmed are candidates,"
says Eugen-Olsen. "And hopefully, archeological findings of the period
may provide further clues and evidence."